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Berylliosis

What Is It, Causes, Treatment, and More

Author: Lily Guo

Editors: Ahaana Singh, Lisa Miklush, PhD, RN, CNS

Copyeditor: Joy Mapes

Illustrator: Jillian Dunbar


What is berylliosis?

Berylliosis is a rare disease caused by prolonged exposure to the chemical element beryllium. Beryllium is a known carcinogen, or cancer causing agent, for both humans and animals, and it is commonly found in factory settings producing springs, gears, and cogs. Berylliosis occurs in 2 to 5% of workers exposed to beryllium and is a systemic disease that results in the formation of abnormal inflammatory nodules, or granulomas, in the lungs and other parts of the body. It is the result of an exaggerated immune system response to beryllium. Acute berylliosis occurs suddenly with a rapid onset, whereas chronic beryllium disease (CBD) develops more slowly and is more common.

What causes berylliosis?

Beryllium exposure is the root cause of berylliosis. Industries that commonly use beryllium include the electronics industry, defense industries (e.g., aviation, weaponry), and metal machine shops. Beryllium can also be found in computer parts, dental appliances, and jewelry-making tools. The element can be inhaled as airborne particles or absorbed through the skin, and the insoluble particles can remain in the body for years. 

Once exposed to beryllium, the body may mount a cell-mediated immune response involving T-cells, a type of white blood cell that has become sensitized to the element. Each exposure leads to the immune system attacking the lungs or skin where the beryllium accumulates. Over time, this can lead to aggregations of white blood cells involved in the immune system’s reaction to foreign particles. Such aggregations of these cells are known as granulomas and can cause pulmonary fibrosis, or scar formation on the lungs. In some cases, it has been demonstrated that some people may have a genetic predisposition for developing CBD once exposed. 

Notably, however, not everyone exposed to beryllium will develop berylliosis. Generally, individuals need to be exposed to significant levels of beryllium over a long period of time to be susceptible. 

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What are the signs and symptoms of berylliosis?

In cases of chronic berylliosis, inflammatory granulomas develop within tissues and organs, which leads to scarring and thickening of the deep lung tissue. The individual may not know they are affected until months, or even years, after their initial exposure. Symptoms of chronic berylliosis include coughing, fever, fatigue, weight loss, chest pain, and shortness of breath. The onset of symptoms can occur at any time from 3 months to 30 years after exposure to beryllium dust. 

On the other hand, acute berylliosis is characterized by severe inflammation of the lungs (i.e., pneumonitis), coughing, and increasing shortness of breath (i.e., dyspnea). The skin and eyes may also be affected in some individuals, causing a burning rash or eye irritation. 

How is berylliosis diagnosed?

To diagnose berylliosis, a clinician may perform a physical examination. Exams may reveal lymphadenopathy, or enlarged lymph nodes, as well as hepatosplenomegaly, or swelling of the liver and spleen. Abnormal lung sounds, such as short, high-pitched clicking sounds called “crackles,” may be heard upon examination. If beryllium was absorbed through the skin, rashes may be present. Occupational history and previous known exposure play a critical role in determining whether or not the definitive diagnosis of berylliosis can be made. 

If berylliosis is suspected, further testing will likely be performed to confirm the diagnosis. A bronchoalveolar lavage (BAL) test may be performed. During a BAL test, a tubular tool called a “bronchoscope” is inserted into a sub-segment of the lung, sterile saline is passed through to the airways, and the saline is collected for inspection. In addition to BAL, a positive beryllium lymphocyte proliferation test (BeLPT) can likewise be indicative of berylliosis. A BeLPT is a blood test in which white blood cells from the affected individual are drawn and mixed with a beryllium solution. If the individual’s immune system was previously sensitized to beryllium, the white blood cells will multiply. 

Imaging studies like chest radiographs and computed tomography (CT) scans may be used, but they are not as specific as the BAL test or BeLPT. Early in the disease, radiographic findings can appear to be normal, while later progressions may reveal interstitial fibrosis, abnormalities of the tissue around the lungs and chest cavity (i.e., pleural irregularities), and swollen or enlarged lymph nodes (i.e., lymphadenopathy), especially of the hilar lymph nodes located on the central portion of the lungs. On CT imaging, ground-glass opacities, or areas that appear hazy, are commonly seen in the lungs of individuals with berylliosis. 

Other tests include arterial blood gas tests, during which blood is evaluated for oxygen and carbon dioxide levels; diffusing capacity for carbon monoxide tests (DLCO or TLCO), which measure the extent that oxygen passes from lungs to blood; and pulmonary function tests. Lastly, a lung biopsy may be conducted to detect granulomatous inflammation. 

How is berylliosis treated?

Although chronic berylliosis is not curable, symptoms can be treated and managed with medications, such as glucocorticoids and immunosuppressive agents. Glucocorticoids are administered at a high starting dose and must be used for several months before the symptoms begin to resolve. The medication is then tapered off to reduce the adverse effects of steroids. If the individual does not respond to glucocorticoids, they may be prescribed immunosuppressive agents, like methotrexate and azathioprine, and monitored regularly with complete blood counts and liver function tests. Immunosuppressive medications can increase the risk of contracting infections, so it is highly recommended that individuals taking immunosuppressants also get vaccinated against influenza and pneumococcal infections

While stopping exposure to beryllium has not been proven to decrease the progression of berylliosis, it is still advised. For those in the early stages of the disease who still have normal lung function and lack clinical symptoms, periodic monitoring with pulmonary function tests, physical exams, and chest radiography is recommended. Additionally, those who smoke must receive smoking cessation counseling to prevent any further damage to lung function. Continuous follow-up with blood tests, chest x-rays, and pulmonary function tests is often recommended for chronic berylliosis. 

Acute berylliosis may be treated with corticosteroid drugs, breathing support (e.g., ventilators), and other supportive treatment to manage the symptoms. With rapid, timely treatment, most individuals recover with no side effects. 

How many people die from berylliosis?

Approximately 1 to 6% of beryllium-exposed employees develop chronic berylliosis, and the mortality rate ranges from 5 to 38% of the cases. The incidence of acute berylliosis is rare due to development of protective measures to reduce occupational exposure; however, the rate of chronic disease occurs at the same rate as when the condition was first recorded in the 1940s.

What are the most important facts to know about berylliosis?

Berylliosis is a systemic disease involving the formation of granulomas after exposure to the element beryllium. It can present as an acute or chronic form of disease, during which the immune system attacks the lungs (after  inhalation of beryllium) or the skin (after direct physical contact). Symptoms include coughing, fever, fatigue, weight loss, chest pain, and shortness of breath. Diagnosis can be made by performing a physical exam to assess for abnormal lung sounds and abnormal lymph nodes, liver, or spleen. A BAL test and BeLPT may also be used to confirm the diagnosis of berylliosis. Treatment may include corticosteroid drugs, glucocorticoids, and immunosuppressive agents, as well as symptom support. The disease is rare, with only 1 to 6% of beryllium-exposed employees developing a chronic form of berylliosis. 

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Related links

Restrictive lung diseases
Diffuse parenchymal lung disease: Clinical practice
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Resources for research and reference

Maier, L. (Ed.). (2016). Beryllium lymphocyte proliferation test. In National Jewish Health. Retrieved December 22, 2020, from https://www.nationaljewish.org/conditions/beryllium-disease/diagnosis/beryllium-lymphocyte-proliferation 

Sizar, O., & Talati, R. (2020, June 30). Berylliosis. In StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470364/